Touch screen based cognitive testing for rats and mice - Bussey
Submitting InstitutionUniversity of Cambridge
Unit of AssessmentPsychology, Psychiatry and Neuroscience
Summary Impact TypeTechnological
Research Subject Area(s)
Medical and Health Sciences: Neurosciences
Psychology and Cognitive Sciences: Psychology
Summary of the impact
In 2009 Tim Bussey and Lisa Saksida commercialised novel apparatus and
control software for computer-automated behavioural testing of rats and
mice, reducing the time and user-hours required to generate data; and
yielding improved performance levels and opportunities for translation
whilst also reducing variability. The apparatus is sold with a battery of
purpose-designed cognitive tests that parallel those used to assess
cognition in patients (e.g., CANTAB). This has had impact as follows: (1)
sales: over 400 units; (2) preclinical research: because of its potential
for translation of the tasks, the apparatus is influencing how
pharmaceutical companies conduct CNS research; (3) spinoff industry:
contract research organisations now include touchscreen-based cognitive
assays in their services.
Bussey (Lecturer 2000; Senior Lecturer 2003; Reader 2010; Professor,
2013) and Saksida (Lecturer 2001; Senior Lecturer 2007; Reader, 2012) in
the Department of Psychology specialise in the assessment of cognition in
animals. In 2000, Bussey and Saksida started their laboratory in
Cambridge, and a consequence of their research programme into fundamental
aspects of cognition has been the development of a touchscreen-based
cognitive testing system for preclinical rodent models of CNS disease. The
major advantage of using a touchscreen interface is that it is identical
to the human equivalent, enabling very similar (and in some cases
identical) paradigms and methodologies to be used when studying
preclinical and patient populations.1,2 The system was
originally highly promising but difficult to implement. To bring this
product to market and into the laboratories of academia and Big Pharma,
a large amount of experimentation was required, as follows:
(1) Production of a physical prototype that was designed to make the
touchscreen system commercially viable and user-friendly, on the basis of
research done in Bussey and Saksida's laboratory. For example, the chamber
has a unique trapezoidal wall shape to focus the animal's attention;
specialized infrared touchscreens that are sensitive to rodent nosepokes
whilst not disturbing the animal; and a unique configurable design in
which the food delivery system can be moved to allow for a wider variety
of cognitive tests. These innovations needed to be tested with
experimental models using both rats and mice, to ensure robustness and
reliability. Bussey and Saksida have published papers describing over 30
such experiments since 2000. Although the general features of the
apparatus have proven robust, many experiments are ongoing which are
enabling more subtle modifications such as optimization of the nature of
the shapes presented on the screen, the design of the `mask' that directs
the animals' response to the screen and the best food reward to maximize
(2) Saksida wrote the software that was used to carry out many
experiments to test that the tasks can be learned by animals in a
reasonable amount of time, and to run experiments needed to validate the
tasks. Then the control software was expanded to make it possible for
non-specialist users to run the system, change parameters and collect
data. Again, a large number of experiments were run to ensure that the
software is bug-free and user-friendly. Then, the software had to be
re-coded by Campden Instruments to a professional standard; again,
experiments in our laboratory were required to ensure that the programs
run properly. This process continues as new tasks are developed.
(3) Bussey and Saksida developed and validated a suite of tasks to
parallel those used in human test batteries such as CANTAB, developed for
human use. There is now a battery of about 15 tasks tapping into various
aspects of cognitive function such as attention, memory and visual
discrimination. All of these tasks had to be validated both in terms of
behaviour (ensuring that the animals behave as they should when parameters
are altered) and the brain (i.e., that the task relies on the right brain
circuits) involving considerable additional experimentation, all of which
has so far been carried out in the Bussey/Saksida laboratory or via direct
collaboration.4,5 Since commercialization in 2009, independent
papers validating touchscreen tasks have also been published.
(4) As the bulk of the work leading up to this project had involved rats,
Saksida and Bussey developed a version of the touchscreen apparatus
suitable for mice. Mice present particular problems for an endeavour such
as this. First, for anatomical and physiological reasons, apparatus for
the mouse has to have different features from that used in the rat and, as
described above, this had to be tested in actual mice. Secondly, unlike
rats, strains of mice vary wildly in their behavioural response to tasks
like these. Bussey and Saksida had to test a number of mouse strains to
ensure that they could be used with the apparatus. Finally, mouse models
of disease, e.g., Huntington's or Alzheimer's mice, present with
particular challenges such as motor and motivational changes and so these
models had to be tested for compatibility with the apparatus and tasks.6.
On-going research by Bussey and Saksida continues to develop the apparatus
References to the research
1. Bussey, T.J., Holmes A., Lyon, L., Mar, A.C., McAllister, K.A.L.,
Nithianantharajah, J., Oomen, C.A. & Saksida, L.M. (2012). New
translational assays for preclinical modelling of cognition in
schizophrenia: the touchscreen testing method for mice and rats. Neuropharmacology,
Special Issue on Schizophrenia, 62(3):1191-1203.
2. Nithianantharajah, J, Komiyama N.H., McKechanie, A.,
Johnstone, M., Blackwood D.H., St Clair, D., Emes R.D., van de Lagemaat
L.N., Saksida L.M., Bussey T.J. * & Grant, S.G.N. *
(2013) Synaptic scaffold evolution generated components of vertebrate
cognitive complexity, Nature Neuroscience, 16 (1):16-24.
3. Bussey, T.J., Padain, T.L., Skillings, E.A., Winters, B.D., Morton,
A.J., & Saksida, L.M. (2008). The touchscreen cognitive testing method
for rodents: How to get the best out of your rat. Learning &
Memory, 15, 516-523.
4. Romberg C., Bussey T.J., Saksida L.M. (2011). Attentional impairments
in the triple transgenic mouse model of Alzheimer's disease: Rescue with
donepezil (Aricept). Journal of Neuroscience, 31, 3500-3507.
5. Talpos, J., Winters, B.D., Dias, R., Saksida, L.M. & Bussey, T.J.
(2009). A touchscreen-automated paired-associate learning (PAL) task
sensitive to pharmacological manipulation of the hippocampus: a
translational model of cognitive impairments in neurodegenerative disease.
6. Morton, A.J., Skillings, E., Bussey, T.J. & Saksida, L.M. (2006).
Measuring cognitive deficits in disabled mice using an automated
interactive touchscreen system. Nature Methods, 3, 767. Awarded
the "highly commended" prize in the NC3Rs 3Rs competition, 2008.
Details of the impact
The Bussey-Saksida Rodent Touchscreen Chamber was licensed to Campden
Instruments (CI; parent company Lafayette Instruments) on 1 February 2008;
and the company launched two commercial products, distinct chambers for
rat and mouse, in early 2009. Additional series of tests developed by Drs
Bussey and Saksida were the subject of further licenses on 24 December
2009 and 1 July 2010. Further task development continues by Bussey and
Saksida, and as new tasks are validated and published they are licensed to
Campden Instruments. Drs Bussey and Saksida continue working with this
company to market the touchscreen chambers and to advise purchasers on
their setup and utilisation.
The impact on Campden Instruments has been highly beneficial.1,2,3.
The touchscreen chambers represent a significant increase in sales for the
company (they have added about £400-500K p.a. to Campden's turnover over
the last 2-3 years); broadening its portfolio in the behavioural
marketplace; and enabling this to become an export-led company. As a
result, Campden Instruments has added three operatives to its factory
workforce. There is a clear link between this commercial success and the
work done by Bussey and Saksida at Cambridge, specifically: (1) the
development of the prototype equipment in the Bussey-Saksida laboratory,
combined with Campden Instruments' engineering expertise leading to cost
reduction and the development of the high sensitivity touchscreens; and
(2) the on-going development and validation of the tasks.
(2) Preclinical Research: through the opportunity for translation of
the tasks, the apparatus has influenced how pharmaceutical companies
conduct CNS research.
The system is attractive to pharmaceutical companies because of the high
level of reproducibility and comparability of results between different
chambers and in different geographic locations. Other beneficial features
are the translational potential including the fact that better preclinical
data should lead to fewer drug failures during clinical trials. In
addition, the high throughput and automated nature of the system are
beneficial in a commercial setting, as is the fact that the system is user
friendly and relatively failsafe for non-experts in rodent behaviour. By
March 2013, 138 rat chambers and 302 mouse chambers had been sold
worldwide to both academic institutions and pharmaceutical companies.
Two very large research consortia have featured this system as a core
component of their programmes. The NEWMEDS consortium, one of the largest
ever academic-industry collaborations, was funded in September 2009 for 5
years by the Innovative Medicines Initiative to find new methods for the
development of drugs for schizophrenia and depression. Ten major
biopharmaceutical companies are involved, including AstraZeneca, Eli Lilly8,
Janssen Pharmaceutica, Lundbeck A/S, Novartis, Orion, Pfizer, Roche,
Servier and Abbott. The project focuses on developing new animal models to
identify innovative and effective drugs for schizophrenia. The behavioural
test battery designed to characterize animal models of schizophrenia
extensively involves Bussey-Saksida touchscreen tasks. PharmaCog, a sister
IMI-funded initiative to NEWMEDS targeting Alzheimer's Disease, also has a
significant rodent touchscreen component. Academic and commercial members
of the consortium have purchased Bussey-Saksida chambers for use in
underpinning project work.
(3) Spinoff industry: Contract Research Organisations have included
touchscreen-based cognitive assays in their services.
Examples include Synome4 who indicate on their website that:
`The cognitive characterisation of mouse models of human brain disorders
is important for their use in screening potential therapeutic agents.'
Synome offers a battery of touchscreen cognitive tasks, designed in
consultation with both Bussey and Saksida, who act as external advisors to
The company Transpharmation provides translational pre-clinical
pharmacology services to the pharmaceutical and biotechnology industry,
with the aim of better understanding potential new medicines as they
transition into the clinic. They also offer a battery of Bussey-Saksida
cognitive tests6, and Bussey provided consultancy to this
company when they were initiating their services7.
(4) Specialist advisory role in maximising the translation of
effective therapies from animal models to clinical practice.
For example, the touchscreen system featured and was demonstrated by
Bussey and Saksida at the following:
July, 2012, Washington DC: National Institutes of Health Opportunity
Network workshop, Improving Animal Models of Human Behavioral and
Social Processes. The purpose of the workshop was to discuss
strategies for improving the design and construction of animal models for
understanding human behavioral and social processes
March, 2012, Washington DC: Institute of Medicine Forum on Neuroscience
and Nervous System Disorders workshop: "Improving Translation of Animal
Models for Nervous System Disorders".
In addition, since development of the mouse version, commercial interest
in the system has been very high. It has been featured as a key cognitive
testing method in `What's Wrong With My Mouse: Behavioral phenotyping of
transgenic and knockout mice' (Crawley, 2007), the standard guide to
behavioural testing for mouse researchers including those in Industry. It
has also been featured in a number of popular articles in high-impact
journals reaching a broad and non-academic readership, including Nature.
5) Impact on the 3Rs
The 3Rs are a widely accepted ethical framework for conducting scientific
experiments using animals humanely: 1. replacement — use of non-animal
methods; 2. reduction — methods which reduce the number of animals used;
and 3. refinement — methods which improve animal welfare. Our paper in Nature
Methods (Ref 6, section 3) was awarded the `highly commended' prize
in the NC3Rs 3Rs competition, 2008.
Sources to corroborate the impact
- Letter from Director, Campden Instruments
- Product page: www.campden-inst.com/product_detail.asp?ItemID=1970
- CamTouch technical standard: http://www.limef.com/downloads/camtouch.pdf
from Chairman, Synome
- Referee; Managing Director, Transpharmation
- Referee; Senior Research Scientist, Eli Lilly